The biology of how the brain forgets

Our brain tends to forget things that we wish we would always remember. And yet, it cannot forget certain things we wish never occurred and existed. How does your brain forget? And, can your brain forget on purpose? By nature, the human brain forgets. Inopportunely, the biological mechanism underlying this brain process is poorly understood. Only few studies shed light on this aspect. In May 2012, scientists attempted to explain the molecular biology of active elimination of memories on their report. In September 2018, another team of researchers identified the parts of the brain associated with forgetting. Based on brain frequencies, they analyzed how the human brain voluntarily forgets.

Molecular biology of forgetting

In 2012, an independent research team from the Scripps Research Department of Neuroscience attempted to understand the molecular biology of active forgetting.1 To do so, they used fruit flies (Drosophila) as key model since this species is often used for studying memory. Accordingly, they found that a small subset of dopamine neurons regulated the acquisition as well as the forgetting of memories. In other words, they saw that the neurons that acquired memory on one hand also eliminated the memory on the other hand. Notably, they identified the two dopamine receptors involved, i.e. dDA1 and DAMB.

In this case, dopamine, a neurotransmitter, seemingly performs dual, yet opposing, roles. At first, the dopamine activates the dDA1 receptor of a neuron. In effect, the neuron begins forming memories. However, the same neuron sends out signal via another dopamine receptor, DAMB. As dopamine binds to the DAMB receptor, it activates the receptor. As a result, it triggers events that lead to the forgetting of the recently acquired memory (provided that the memory has not been consolidated yet). A process, called consolidation, protects important memories from being forgotten. In essence, while memory actively forms, a dopamine-based forgetting mechanism works as well. Unless the brain reckoned the memory as important, it erases the forming memory.

Forgetting on purpose

In September 2018, researchers from Ruhr-Universität Bochum and the University Hospital of Gießen and Marburg collaborated with researchers from Bonn, the Netherlands, and the UK.2 In brief, they identified the parts of the brain involved in the process of voluntary forgetting. In particular, these brain areas include the prefrontal cortex and the hippocampus, the brain region associated with memories.

In this recent study, the researchers found that the prefrontal cortex regulates the activity in the hippocampus. One of the leaders of the team, Carina Oehrn, explicated that the prefrontal cortex suppressed hippocampus activity. Further, she noted that the frequency changed. Accordingly, the difference in frequency caused the currently processed information to cease from being encoded. They referred to this frequency as the forgetting frequency.2

Forgetting – crucial to health

A Marine attended art therapy to relieve post-traumatic stress disorder painted this mask. Credit: Work by Cpl. Andrew Johnston, and released by the United States Marine Corps.

As much as recalling is important, forgetting certain things is pivotal to mental and emotional well being. We inherently forget on purpose. Imagine remembering all – both good and bad. Not only we would have to deal with information overload but we would also be long exposed to feelings associated with those memories.

Post-traumatic stress disorder, regarded as a mental disorder, develops when a person has gone through a traumatic event. People with this condition face higher risks of inflicting self-harm, or worse, committing suicide.3 Hyperthymesia, a condition wherein an individual can extraordinarily recall much of one’s life in vivid and perfect detail, can be off-putting and distressing to the affected individual. Based on one such case, the patient recounted how the ability to remember constant, uncontrollable chain of memories could be exhausting and a burden.4

More research

The metaphorical inability to forget hinders a person to move on and focus on the tasks at hand. Traumatic events seem to be ingrained deeply in mind and soul. For instance, loss of a loved one, warfare, and sexual assaults prove to be difficult to ignore. Thus, we need more insights on the neuro- and molecular biology of forgetting. More studies could help shape up future therapeutic intervention. It may not necessarily lead to the absolute incapacity to recall. But, hopefully, it can help set aside spiteful memories. In that way, affected individuals could be freed from the traps of the past, and help them live life with a sanguine hope for a future.

Porphyromonas gingivalis is a bacterium commonly associated in periodontitis a chronic inflammatory disease in the oral cavity. Periodontium is composed of periodontal ligament, cementum, alveolar bone and gingiva. Porphyromonas gingivalis is a gram-negative bacterium that contains toxic components. It is characterized by the presence of edema and destruction of tissue supporting the teeth. In which periodontal bacteria enters into circulation that leads to bacteremia and system dissemination of bacterial products. Moreover, Porphyromonas gingivalis can promotes systemic effects through expression of inflammatory mediators like pro-inflammatory cytokines. As a consequence it is confirmed to be associated with systemic diseases such as diabetes, respiratory disease and cardiovascular disease.

Potential effects of Porphyromonas gingivalis

Neurodegenerative diseases have been recognized as the major cause of cognitive and behavioral damage. It is known that peripheral infections could activate microglial cells within the nervous system enhancing development of neurodegeneration. Thus, the inflammatory molecules in the brain could be enhanced by periodontitis that increase inflammatory levels promoting the development of Alzheimer’s disease. In this particular research Porphyromonas gingivalis infection may impair cognition by elevating expression of pro-inflammatory cytokines. It is also shown that the infected mice displayed impaired memory and learning abilities. Elevated levels of pro-inflammatory mediators in the blood can lead to direct or indirect transport to the brain.

Periodontal infection caused by Porphyromonas gingivalis promotes neuro-inflammatory response via releasing pro-inflammatory cytokines. In which inflammation induces alterations in neurovascular functions causing increased in blood brain barrier permeability and aggregation of toxins. In brain trauma, infection and presence of endogenic abnormal protein aggregates can activate secretions of TNF-α. That plays a pivotal role in the development and functions of central nervous system. Moreover, aging is also associated to chronic inflammation which exerts additional stress to the brain nerve cells. Additionally, during systemic inflammation the functions of the blood-cerebrospinal fluid barrier were also significantly affected.

Therefore, Porphyromonas gingivalis periodontal infection may induce age-dependent brain inflammation. Also periodontitis can cause memory impairment which has a similar effect on the development of Alzheimer’s disease. Furthermore, aging is the major risk factor of Alzheimer’s disease and is correlated with elevated glial responsiveness. And in due course might increase the brain’s susceptibility to injury and disease.

Newly identified human brain neuron may have unique genetic signature

Dubbed as “rosehip neuron“, a new brain neuron recently discovered is unique based on its morphology and the set of genes it activates. Neuroscientists recently uncovered this new type of neuron from postmortem human brain samples. They presumed that this rosehip neuron occurs in the brain of humans but not in rodents.

Rosehip neurons found in human brains

What makes human brain special? What sets it apart from other animal brains? Humans have this sort of consciousness and intelligence that make them different from other species. Apart from the complexity and the size of the human brain, its cellular components seem to be different from that of the other animals. Neuroscientists found rosehip neurons in human brain. These cells have not yet been observed in the brains of mice and other well-studied laboratory animals. Researchers reported this recent discovery in Nature Neuroscience.1 Nevertheless, they were fast to warn not to make haste assumptions. The rosehip neurons may not be unique to humans. More studies are on the way to confirm it.

What their findings implicate is the suitability of rodent brains as experimental models. Rodent brains lack such neurons. Thus, they may not be fit as laboratory models, especially when one tries to understand human neurologic diseases and how the brain works.

Current info on human rosehip neurons

Since rosehip neurons are a recent discovery, there is currently little information about them. What the neuroscientists know is they appear bushy. In fact, their bushy appearance accounts for their name “rosehip“. Rosehip originally refers to the accessory fruit of the rose plant. The rosehip neuron looks like the accessory fruit of the rose after petals are shed.

Researchers discovered the rosehip neurons from the top layer of the cortex of the brain from the postmortem brains of two men in their 50s. The rosehip neuron belongs to a group of inhibitory neurons. This means that it works by inhibiting other neuronal activity in the brain.

Researchers from the Allen Institute collaborated with the J. Craig Venter Institute. They found that the rosehip neurons seemed to have a different genetic signature. The rosehip neurons turned on a unique set of genes. They also formed synapses with pyramidal neurons. Pyramidal neurons are a different type of brain cells named after their shape.

Future research on rosehip neurons

Researchers have yet to fully recognize the purpose and importance of rosehip neurons in the human brain. In doing so, they may gain a significant insight regarding their role in neurologic function and diseases. They also aim to check the presence of rosehip neurons in other human brain parts as well as in the brains of other animals. Details on their recent work on rosehip neurons is published in Nature Neuroscience.2

Brief Diversions Help Keep Selective Attention in Top-notch

The ability to focus one’s attention on a specific point of interest for a given time is referred to as selective attention. Imagine a scenario wherein you can pay attention to everything. That would lead to information overload. Selective attention enables an individual to react to certain stimuli from among those occurring simultaneously. This ability is crucial particularly when you need to focus on a task you need to finish before the time is up. You tend to put much of your attention to your target and then ignore potential distractions.

Neurobiology of selective attention

Selective attention is one of the neural functions of the brain. The neurons relay the information from one neuron to the next by releasing neurotransmitters, such as acetylcholine, at the synapse. The neurons responsible for our capacity to focus are found in the lateral prefrontal cortex.1 They are also responsible for suppressing potential distractions in the background. For more neurobiological aspect and potential therapeutic targets, read Selective Attention – neurobiology and potential therapeutics.

Selective attention and inattentional blindness

While we can choose which of the things to focus on and which ones to ignore, there are also instances wherein we tend to overlook things beyond our will. One of the possible consequences of selective attention is inattentional blindness, which is the phenomenon of not being able to perceive things although they are just right in front of our eyes. Because we are focused on one thing, there is a tendency that other things escape us. For instance, you might not notice the tiniest details on your essay (e.g. misspelled words) or missed key information from a reference book.

Inattentional blindness can be perfectly demonstrated through Daniel Simons and Christopher Chabris’ invisible gorilla test. The test is a video of two basketball teams in which the viewer has to count how many times the ball is tossed around to the team members. The viewer would likely be so busy counting that the person in a gorilla suit walking back and forth on the background would easily go unnoticed. Because of selective attention, we are inclined to filter things out. We might even think that we saw everything but, in fact, we only see what we want to see. Thus, letting other salient details to slip out while on selective attention is not unusual.

Brief diversions improve selective attention

Imposing short and momentary breaks helps to rest mentally from sustained stimulations, and thereby, possibly keep up excellent selective attention.

One could easily surmise that selective attention and distractions should never go together when one wants to complete a highly demanding task. However, this seems to be the opposite based on what Atsunori Ariga and Alejandro Lleras from University of Illinois at Urbana-Champaign found in their study.2 Repetitive tasks that required prolonged selective attention could wind up to diminished quality in performance. The researchers presumed that diminishing attention per se was not the culprit to a poor performance but the constant stimulation happening in the brain. Lleras explained: “Constant stimulation is registered by our brains as unimportant, to the point that the brain erases it from our awareness.” What their study implicates is to impose short and momentary breaks to rest mentally from sustained stimulations. Brief breaks, as they proposed, will help to stay focused while doing long, arduous tasks, such as studying before an exam.2

Perhaps, we can all agree that there are times when selective attention can be a cinch and then there are also times when it is simply impossible. We can get easily distracted. There are just so many factors that prevent us from focusing on a daunting task. An emotional turmoil, for instance, is one such distraction that can be difficult to overcome. Nevertheless, these studies open up to possibilities how diversions and distractions can be put to use to uphold selective attention to tasks that need to be done over prolonged periods of time.

— written by Maria Victoria Gonzaga

References:1 McGill University. (2015, January 7). Having a hard time focusing? Research identifies complex of neurons crucial to controlling attention. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2015/01/150107081701.htm2 University of Illinois at Urbana-Champaign. (2011, February 8). Brief diversions vastly improve focus, researchers find. ScienceDaily. Retrieved June 5, 2018, from www.sciencedaily.com/releases/2011/02/110208131529.htm

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Selective Attention – neurobiology and potential therapeutics

Selective attention refers to the ability of an individual to focus. We can choose what to pay attention to and then ignore all else unless it is something worthy of our attention. Think about this: a day before the final submission of an essay project, you would probably be pressured into doing nothing else but to read and write to finish the task as soon as possible. You would probably clear yourself off from all the conceivable distractions like a favorite TV series or a video game. You might even go as far as going to a place secluded, away from all irrelevant noise and people just so you could focus and finish it on time. Yes! That is basically how selective attention works.

Selective attention – the neural basis

So how about the neural basis of selective attention? Our brain is made up of two major types of cells: neurons and glial cells. The glial cells mainly are for supportive functions whereas the neurons play a part in cell-to-cell communication, particularly for conducting nerve impulses. The information is relayed from one neuron to another, much like a text message relayed through an instant messaging app from the sender to the recipient. In this regard, the acetylcholine takes the role of the app that relays the nerve impulse (the message) from one neuron to the next. Besides acetylcholine, other brain chemical systems may also be at work for selective attention to ensue. A research on the attention mechanisms in a primate model revealed that glutamate coupled to NMDA receptors was found to be involved as well. 1 Thus, in order to elicit focus and attention, the message has to be essentially loud and clear.

Improving selective attention – potential therapeutic targets

Selective attention refers to the ability of an individual to focus. We can choose what to pay attention to and then ignore everything else unless it is something worthy of our attention.

Our ability to focus and, at the same time, suppress distraction lies on the neurons located in the lateral prefrontal cortex of our brain.2 The neurons in this brain region do not only serve as the selective attention machinery but also as the anti-distraction system.3 This means that while they enable us to pay attention to important matters they also suppress distractions in the background. This could serve as a potential therapeutic target for producing a drug that could help improve selective attention.

In another research, a team of scientists identified three structures, namely cortex, thalamus, and thalamic reticular nucleus (or TRN, a thin layer of neuronal cells surrounding the thalamus.), that apparently formed neuronal circuits in mouse brain models.4 These neuronal circuits seemed to control the selective attention and sensory processing in the animal’s brain. In essence, the sensory information initially passes through the thalamus where it is determined as to whether relevant or not. It, then, has to pass through the TRN before it can reach the cortex for processing. When they inactivated the ErbB4 protein in the TRN, they found that the selective attention of the mice amid distractions was greatly affected. This could, therefore, be another therapeutic aspect to consider.

Attention Deficit Disorder (ADD) – impaired selective attention

Attention deficit disorder or ADD is a neurologic disorder associated with impaired selective attention. An individual with ADD is struggling to focus and easily gets distracted. As a result, completing salient tasks can be a challenge because the attention is easily diverted to other stimuli that are irrelevant to the initial task. ADD may or may not involve hyperactivity. The condition in which the person experiences not only an impaired selective attention but also manifests excessive activity and behavioral problems inappropriate for one’s age is referred to as attention deficit hyperactivity disorder or ADHD. People with ADD without hyperactivity may not necessarily show behavioral problems. Nonetheless, their attention shifts to other extraneous activities resulting in slow-paced, poor performance.

A deeper understanding on the neurobiological basis of selective attention is essential because they could serve as potential therapeutic targets. Individuals with attention deficit disorder are just one of those who might benefit. Without focus, we would hardly be able to keep up with the simple chores to the more challenging undertakings. A functional selective attention does have a crucial role in enabling us to complete a task in time.

A Neurobiological Approach to Understanding Human Intelligence

Is human intelligence measurable? … quantifiable? Perhaps, you came across this popular catchphrase purportedly quoted by the genius, Albert Einstein: “Everybody is a genius. But if you judge a fish by its ability to climb a tree, it will live its whole life believing that it is stupid.” One of the most popular methods of measuring intelligence is by intelligence quotient (IQ) tests. The accuracy of the results is highly debatable though. These tests have long been criticized for being not all-inclusive, and therefore may not fully represent human intelligence.

Human intelligence – how the brain works

The brain is one of the most studied parts of the human body and yet scientists are still mystified as to how it completely works and how it hallmarks the uniqueness of human intelligence. An adult human brain is comprised of neurons and glial cells. While the glial cells are primarily for support, the neurons are essential for cell-to-cell communication, particularly for conducting nerve impulses. The neurons are excitable cells with specialized parts (e.g. soma, dendrites and axons), structures (e.g. synapses), and chemicals (e.g. neurotransmitters). In essence, the neuron generates nerve impulses that travel along the axon, resulting in the release of neurotransmitters that bind to the receptors of the dendrites of the target neuron. The ensuing effect may either be excitatory or inhibitory. The integration of these nerve impulses leads to the brain carrying out higher brain functions, such as language, speech, emotions, memory, learning, etc. The brain is truly a spectacular organ in charge of a mélange of tasks epitomizing human intelligence.

An illustration of the process of synaptic transmission in neurons

Human intelligence measured by IQ tests

IQ tests were devised to measure human intelligence based on the ability of an individual to generate answers that rely on reasoning and information, and how quickly. They are used in order to figure out if a person is capable of making quick, knowledgeable, and logical answers, especially in situations requiring immediate solutions. In educational settings, IQ tests help teachers predict which areas a student excels at and which ones a student would need extra help. However, making speculative conclusions based on IQ test results may lead to bias and wrong assumptions. For instance, predicting future success based on IQ or even on human intelligence is not as simple as it seems. It takes perseverance, passion, and sometimes, even luck. What a high IQ could point at is the person’s aptitude for certain realms of human intelligence.

Measures of human intelligence by neurobiological means

3D illustration of the human brain. (Credit: yodiyim)

Apart from IQ test-based measures, other methods have been designed to perceive and measure human intelligence. One of which is the integration of neurobiology. Researchers began to look at the structure of the brain and how it functions. Aki Nikolaidis, a neuroscientist, conducted a study with colleagues. Fluid intelligence was monitored through magnetic resonance spectroscopy on adult volunteers while taking IQ tests. Fluid intelligence is a form of intelligence primarily based not on stored knowledge but on the ability of a person to solve complex problems without prior information. In their study, they identified the specific parts of the brain that were active during fluid intelligence. They found that the predictor of fluid intelligence is located on the left frontal and parietal parts of the brain, independent of the brain size.1 Another recent study suggests that intelligence is inversely proportional to the number of dendrites the individual has. Accordingly, smarter people tend to have fewer brain dendrites, which implies that they have fewer connections between neurons in their cerebral cortex. In other words, the more intelligent a person is, the fewer brain wirings he or she needs for a brain function.2

How the brain works and how it is structured are just a few of the facets that researchers tap to understand human intelligence. Future research insights are crucial in order to methodically define what human intelligence is, and find ways, if not to boost it, keep it fairly functional even in the declining years.

Aluminium in Brain Tissue in Autism

Autism spectrum disorder is a neurodevelopmental conditions caused by different combinations of genetic and environmental influences. The mechanism underlying its etiology and the factors associated at the onset of progression are multi-factorial. Autisms are range of conditions distinguished by unreasonable social skills, difficulty in speech, repetitive behaviors and unique strengths. However, some research study reveals that exposure to aluminum has been implicated in autism spectrum disorder. Wherein, hair used as an indicator of human exposure to aluminum as well as in blood and urine. There were also reports that pediatrics vaccines contain aluminum adjuvant that caused indirect infant exposure to aluminum. Hitherto, no previous records of aluminum in brain tissue. That is why this research study about to identify the aluminum found in the brain tissue.

Aluminum content in autism brain tissue

The aluminum content in brain tissues from the donors diagnosed with autism spectrum disorder is high. Approximately 40% of the brain tissue has the aluminum content and males have higher deposits of aluminum than females. On the other hand, white and grey matter of the brain contains aluminum both intra and extracellular location. Using fluorescence microscopy provides the location of aluminum in the brain tissue. Moreover, the mode of entry of aluminum somehow came from the blood-brain barrier and was then taken by the microglial cells. Interestingly, an inflammatory cell in the vasculature also opens the possibility of entry of aluminum into the brain.

Additionally, atomic absorption spectrometry was used to measure for the first time the aluminum content of brain tissue in autism. Particularly the aluminum was found in frontal, occipital, temporal and parietal lobes of the brain. But the highest value was found in occipital lobe and that could perhaps implicate the cause of autism spectrum disorder.

Therefore, the presence of intracellular aluminum associated with non-neuronal cells is a notable observation in autism brain tissue. Which is also offers insights about the origin of aluminum in brain and the putative role in autism spectrum disorder. Overall, the presence of aluminum in meninges, inflammatory cells, vasculature, grey and white matter possibly linked the etiology of autism spectrum disorder.

Hubs in the Human Fetal Brain Network

Human brain contains highly connected regions called “hubs” that are very important for efficient neuronal signaling and communication. In mature individual hubs are constantly found in precuneus, cingulate gyrus, frontal cortex and interior parietal regions. Evidences reveal that because of this highly functional human brain, the hubs support information integration for complex cognitive function. In line with this, abnormal hubs have been implicated to various neurological brain disorders. So the central role of hubs in human brain at the beginning of human life is valuable. Since, it offers insight about the origins of psychiatric and developmental disorders of the human brain at the later life.

Location of hubs in fetal human brain

Hubs were located in cerebellum, inferior temporal gyrus, angular gyrus, precentral gyrus, primary visual cortex and medial temporal lobe. Several hubs found in sensory and motor brain areas. Overall, more hubs were observed in the left rather than the right hemisphere suggesting asymmetry of hub association. Also hubs found in areas close to adult facial fusiform and homologous areas. Taken together, results suggest that hubs emerge before birth and serves as the important building block in human brain development.

This is the first research study about the functional hubs in human brain prior to birth. It reveals that within the organization of fetal brain there are hubs that are already important for neural efficiency. Particularly in both primary and association brain regions shows centrality in network before birth. The fetal brain network is not wired exclusively for perception but instead, prepare the brain for higher cognitive functioning in later life.

Hence, the network organization of fetal human brain contains hubs that are central to the architectural neural circuitry. Hubs were identified in motor and visual areas as well as in association cortices of the fetal brain. Interestingly, many hubs were localized in cerebellar region supporting the idea that hubs emerge in areas early to myelinate. It is hypothesized that, because of high centrality in network, hub regions generates neural activity that stimulates myelin. Additionally, hubs are significant for global efficiency of the fetal human brain network for higher cognitive functioning and serve as biomarkers for neurodevelopmental disorders.